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Global Identification of Genes Related to Nutrient Deficiency in Intervertebral Disc Cells in an Experimental Nutrient Deprivation Model
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| Title: | Global Identification of Genes Related to Nutrient Deficiency in Intervertebral Disc Cells in an Experimental Nutrient Deprivation Model |
| Authors: | Sudo, Hideki Browse this author →KAKEN DB | | Yamada, Katsuhisa Browse this author | | Iwasaki, Koji Browse this author | | Higashi, Hideaki Browse this author | | Ito, Manabu Browse this author | | Minami, Akio Browse this author | | Iwasaki, Norimasa Browse this author |
| Issue Date: | 8-Mar-2013 |
| Publisher: | Public Library of Science |
| Journal Title: | PLOS ONE |
| Volume: | 8 |
| Issue: | 3 |
| Start Page: | e58806 |
| Publisher DOI: | 10.1371/journal.pone.0058806 |
| Abstract: | Background: Intervertebral disc degeneration is a significant cause of degenerative spinal diseases. Nucleus pulposus (NP) cells reportedly fail to survive in large degenerated discs with limited nutrient availability. Therefore, understanding the regulatory mechanism of the molecular response of NP cells to nutrient deprivation may reveal a new strategy to treat disc degeneration. This study aimed to identify genes related to nutrient deprivation in NP cells on a global scale in an experimental nutrient deprivation model. Methodology/Principal Findings: Rat NP cells were subjected to serum starvation. Global gene expression was profiled by microarray analysis. Confirmation of the selected genes was obtained by real-time polymerase chain reaction array analysis. Western blotting was used to confirm the expression of selected genes. Functional interactions between p21(Cip1) and caspase 3 were examined. Finally, flow cytometric analyses of NP cells were performed. Microarray analysis revealed 2922 differentially expressed probe sets with >= 1.5-fold changes in expression. Serum starvation of NP cells significantly affected the expression of several genes involved in DNA damage checkpoints of the cell cycle, including Atm, Brca1, Cdc25, Gadd45, Hus1, Ppm1D, Rad 9, Tp53, and Cyclin D1. Both p27(Kip1) and p53 protein expression was upregulated in serum-starved cells. p21(Cip1) expression remained in NP cells transfected with short interfering RNA targeting caspase 3 (caspase 3 siRNA). Both G1 arrest and apoptosis induced by serum starvation were inhibited in cells transfected with caspase 3 siRNA. Conclusions/Significance: Nutrient deprivation in NP cells results in the activation of a signaling response including DNA damage checkpoint genes regulating the cell cycle. These results provide novel possibilities to improve the success of intervertebral disc regenerative techniques. |
| Rights: | http://creativecommons.org/licenses/by/3.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/52920 |
| Appears in Collections: | 北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 須藤 英毅
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